Summary

Mucopolysaccharidosis type VII (MPS VII) is a very rare lysosomal storage disease belonging to the group of mucopolysaccharidoses. Less than 40 patients with neonatal to moderate presentation have been reported since the initial description of the disease by Sly in 1973. However, the frequency of the disease may be underestimated as the most frequent presentation is the antenatal form, which remains underdiagnosed. Clinical signs are extremely variable: there are prenatal forms with non-immune hydrops fetalis, and severe neonatal forms with dysmorphism, hernias, hepatosplenomegaly, club feet, dysostosis, severe hypotonia and neurological disorders that ultimately lead to profound intellectual deficit and small stature in patients that survive. Finally, there are also very mild cases that are discovered during adolescence or adulthood following presentation with thoracic kyphosis. The disease is caused by beta-D-glucuronidase deficiency, which leads to accumulation of several glycosaminoglycans (dermatan sulfate (DS), heparan sulfate (HS), and chondroitin sulfate (CS)) in lysosomes. The causative gene has been located on 7q21-q22 and more than 40 mutations have been identified. Transmission is autosomal recessive. Diagnosis is suspected after detection of increased levels of urinary glycosaminoglycan (either CS alone or CS+HS+DS) excretion, although this sign may be absent in adult forms. Diagnosis is confirmed by demonstration of beta-D-glucuronidase deficiency in cultured leucocytes or fibroblasts. Pseudodeficient alleles make mild forms more difficult to identify and prenatal diagnosis difficult. Differential diagnosis includes other types of MPS and oligosaccharidosis. The determination of enzymatic activity in leucocytes allows heterozygous individuals to be detected for the severe forms. When the two mutations have been identified in the index patient, the detection of heterozygous relatives can be accurately performed. Diagnosis is essential in forms with in utero presentation in order to avoid the recurrence of pregnancies leading to in utero death or to late termination of the pregnancy. In the absence of any efficient treatment, prenatal diagnosis (by molecular analysis or measurement of enzyme activity in trophoblasts or amniocytes) is offered to parents with an affected child. Multidisciplinary management allows adapted symptomatic treatment, which is essential for improving the quality of life of the patients. In late-onset forms, treatment is mainly orthopaedic. Bone marrow transplantation has been attempted for one mild case. Multiple assays of other specific treatments are being performed in animal models: allogenic bone marrow transplantation, gene therapy and enzyme replacement therapy (with recombinant enzyme or intraperitoneal implants of autologous genetically modified fibroblasts or ``neo-organs''). Prognosis is poor for antenatal forms, most often leading to death in utero. Neonatal and childhood forms have a very limited life expectancy, whereas milder forms have a prolonged survival.

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